Case Report: High-Dose Methylphenidate for Adult ADHD

Attention deficit hyperactivity disorder (ADHD), once thought to exclusively affect children and adolescents, is not "outgrown" when children become adults. About two-thirds of children diagnosed with ADHD continue to experience its symptoms in adulthood.1,2

In children, the core symptoms of the disorder are inattention (distractibility), hyperactivity, and impulsivity. Symptoms change with the advent of adulthood, with a decrease in hyperactivity. But inattention, impulsivity, and disorganization remain present, causing impairments in functioning both in domestic and in employment/academic settings.3

Adults with ADHD generally have lower incomes, greater difficulties in personal relationships, more instability in employment and academics, and higher rates of car accidents.3 ADHD is highly comorbid with many other psychiatric conditions, including depression and anxiety.4,5 In particular, several studies have shown a strong comorbidity between ADHD and obsessive-compulsive disorder (OCD).6,7

Stimulant medication is usually the first-line ADHD treatment in both the adult and the pediatric populations. In adults, methylphenidate (MPH: Concerta, Daytrana, Focalin, Metadate CD, Methylin, Ritalin) is efficacious when administered in weight-adjusted doses equivalent to those used in children.8

MPH is available in short- and intermediate-acting preparations, as well as slow-release and long-acting ones. Immediate-release MPH reaches peak plasma concentration after two hours and decreases thereafter, necessitating administration several times a day.9 Long-acting formulations, such as once-daily osmotic release oral system (OROS) MPH, improve adherence and demonstrate efficacy similar to that of an immediate-release dose of MPH.

The NHS National Institute for Health and Clinical Excellence (NICE) 2008 guidelines for treatment of adult ADHD set the maximum dose at 100mg of MPH/day.10 However, some patients do not achieve symptom remission at that dose. Liebrenz et al present a case report of a 38-year-old man with comorbid symptoms of ADHD and OCD who remained symptomatic until the was treated with an extremely high dose of MPH (378mg/day).11

The patient was diagnosed with ADHD at age 9 and was treated with a variety of stimulants, including MPH and sustained-release MPH daily. At age 13, these agents were discontinued, and he was switched to desipramine, until, at age 18, symptoms of OCD developed, and clomipramine 75mg was added to his regimen, along with counseling.

Symptoms of hyperactivity and inattention persisted, and the patient resumed taking MPH (60mg/day) at age 22, three years after entering college. He was unable to finish college, due to difficulties in focusing, and several attempts to obtain a secondary degree in the United States, Great Britain and Switzerland also failed.

For unknown reasons, he did not receive further stimulant medication until age 32, when he started taking immediate-release MPH (60mg/day) to reduce distractibility at his new-found job as a sales clerk. Although it was somewhat effective, improvements were not sustained through the day, so during the following 14 months, he began to use MPH excessively, both orally and rectally, at doses of 4,800 to 6,000mg/day.

At age 34, he began treatment at the Outpatient Clinic for Patients with ADHD at the Psychiatric University Hospital in Zurich, Switzerland, where the authors are affiliated. He was diagnosed with an obsessive-compulsive disorder, as well as combined personality disorder and the diagnosis of ADHD was confirmed. Treatment was begun with fluoxetine (40mg/day) and immediate-release MPH 200mg, which was then increased to 240mg and finally 270mg/day.